[1]	NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). PubMed=2991281 [NCBI, ExPASy, EBI, Israel, Japan] Luskey K.L., Stevens B.; "Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation."; J. Biol. Chem. 260:10271-10277(1985).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Nakajima T., Iwaki K., Hamakubo T., Kodama T., Emi M.; "Human HMG-CoA reductase gene."; Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Rieder M.J., da Ponte S.H., Kuldanek S.A., Rajkumar N., Smith J.D., Toth E.J., Nickerson D.A.; Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). TISSUE=Blood; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 422-888, AND SUBUNIT. DOI=10.1093/emboj/19.5.819; PubMed=10698924 [NCBI, ExPASy, EBI, Israel, Japan] Istvan E.S., Palnitkar M., Buchanan S.K., Deisenhofer J.; "Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis."; EMBO J. 19:819-830(2000).
[6]	X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 426-888. DOI=10.1126/science.1059344; PubMed=11349148 [NCBI, ExPASy, EBI, Israel, Japan] Istvan E.S., Deisenhofer J.; "Structural mechanism for statin inhibition of HMG-CoA reductase."; Science 292:1160-1164(2001).
[7]	VARIANT VAL-638. DOI=10.1038/10290; PubMed=10391209 [NCBI, ExPASy, EBI, Israel, Japan] Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.; "Characterization of single-nucleotide polymorphisms in coding regions of human genes."; Nat. Genet. 22:231-238(1999).
[8]	ERRATUM. Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.; Nat. Genet. 23:373-373(1999).

Comments

FUNCTION: This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis.
CATALYTIC ACTIVITY: (R)-mevalonate + CoA + 2 NADP⁺ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.
ENZYME REGULATION: Inhibited by statins, a class of hypolipidemic agents used as pharmaceuticals to lower cholesterol levels in people at risk for cardiovascular disease because of hypercholesterolemia. Inhibition of HMGCR in the liver stimulates the LDL-receptors, which results in an increased clearance of LDL from the bloodstream and a decrease in blood cholesterol levels. The first results can be seen after one week of use and the effect is maximal after four to six weeks.
PATHWAY: Metabolic intermediate biosynthesis; mevalonic acid biosynthesis; (R)-mevalonic acid from acetyl-CoA: step 3/3 .
SUBUNIT: Homodimer.
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. Peroxisome membrane; Multi-pass membrane protein.

ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name	1
Isoform ID	P04035-1
This is the isoform sequence displayed in this entry.

Name	2
Isoform ID	P04035-2
Note: No experimental confirmation available.
Features which should be applied to build the isoform sequence: VSP_002207.

SIMILARITY: Belongs to the HMG-CoA reductase family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

M11058; AAA52679.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273765; AAG21343.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273754; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273755; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273756; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273757; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273758; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273759; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273760; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273761; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273762; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273763; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AF273764; AAG21343.1; JOINED; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY321356; AAP72015.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC033692; AAH33692.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

A00356; RDHUE.

RefSeq

NP_000850.1; -.
NP_001124468.1; -.

UniGene

Hs.699171

3D structure databases

PDB

1DQ8; X-ray; 2.10 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1DQ9; X-ray; 2.80 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1DQA; X-ray; 2.00 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1HW8; X-ray; 2.10 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1HW9; X-ray; 2.33 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1HWI; X-ray; 2.30 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1HWJ; X-ray; 2.26 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1HWK; X-ray; 2.22 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
1HWL; X-ray; 2.10 A; A/B/C/D=426-888.	[ExPASy / RCSB / EBI]
2Q1L; X-ray; 2.05 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
2Q6B; X-ray; 2.00 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
2Q6C; X-ray; 2.00 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
2R4F; X-ray; 1.70 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3BGL; X-ray; 2.23 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CCT; X-ray; 2.12 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CCW; X-ray; 2.10 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CCZ; X-ray; 1.70 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CD0; X-ray; 2.40 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CD5; X-ray; 2.39 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CD7; X-ray; 2.05 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CDA; X-ray; 2.07 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]
3CDB; X-ray; 2.30 A; A/B/C/D=441-875.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1DQ8; -.
1DQ9; -.
1DQA; -.
1HW8; -.
1HW9; -.
1HWI; -.
1HWJ; -.
1HWK; -.
1HWL; -.
2Q1L; -.
2Q6B; -.
2Q6C; -.
2R4F; -.
3BGL; -.
3CCT; -.
3CCW; -.
3CCZ; -.
3CD0; -.
3CD5; -.
3CD7; -.
3CDA; -.
3CDB; -.

ModBase

P04035.

PTM databases

PhosphoSite

P04035; -.

Enzyme and pathway databases

Reactome

REACT_602; Lipid and lipoprotein metabolism.

Organism-specific databases

HIX0004954; -.

HGNC:5006; HMGCR.

HPA008338; -.

142910; gene+phenotype. [NCBI / EBI]

PharmGKB

PA189; -.

GeneCards

P04035.

Gene expression databases

ArrayExpress

P04035; -.

CleanEx

HS_HMGCR; -.

GermOnline

ENSG00000113161; Homo sapiens.

Ontologies

GO:0005789;	Cellular component: endoplasmic reticulum membrane (traceable author statement from ProtInc).
GO:0008354;	Biological process: germ cell migration (traceable author statement from ProtInc).
GO:0008406;	Biological process: gonad development (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR002202; HMG_CoA_Rdtase_cat.
IPR004554; HMG_CoA_Rdtase_I_cat.
IPR004816; HMG_CoA_Rdtase_I_metazoan.
IPR000731; SSD_5TM.
Graphical view of domain structure.

Gene3D

G3DSA:3.90.770.10; HMG-CoA_red; 1.

PANTHER

PTHR10572; HMG-CoA_red; 1.

Pfam

PF00368; HMG-CoA_red; 1.
Pfam graphical view of domain structure.

PRINTS

PR00071; HMGCOARDTASE.

TIGRFAMs

TIGR00920; 2A060605; 1.
TIGR00533; HMG_CoA_R_NADP; 1.

PROSITE

PS00066; HMG_COA_REDUCTASE_1; 1.
PS00318; HMG_COA_REDUCTASE_2; 1.
PS01192; HMG_COA_REDUCTASE_3; 1.
PS50065; HMG_COA_REDUCTASE_4; 1.
PS50156; SSD; 1.
PROSITE graphical view of domain structure (profiles).

Genome annotation databases

Ensembl

ENSG00000113161; Homo sapiens. [Contig view]

GeneID

3156; -.

KEGG

hsa:3156; -.

NMPDR

fig|9606.3.peg.25409; -.

Phylogenomic databases

HOGENOM

P04035; -.

HOVERGEN

P04035; -.

Other

DrugBank

DB01076; Atorvastatin.
DB01393; Bezafibrate.
DB00439; Cerivastatin.
DB01095; Fluvastatin.
DB00227; Lovastatin.
DB00157; NADH.
DB00175; Pravastatin.
DB01098; Rosuvastatin.
DB00641; Simvastatin.

NextBio

12500; -.

SOURCE

HMGCR; Homo sapiens.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Alternative splicing; Cholesterol biosynthesis; Endoplasmic reticulum; Glycoprotein; Lipid synthesis; Membrane; NADP; Oxidoreductase; Peroxisome; Polymorphism; Steroid biosynthesis; Sterol biosynthesis; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 888`	`888`	`3-hydroxy-3-methylglutaryl-coenzyme A reductase.`	`PRO_0000114419`
`TRANSMEM`	`10 39`	`30`	`Potential.`
`TRANSMEM`	`57 78`	`22`	`Potential.`
`TRANSMEM`	`90 114`	`25`	`Potential.`
`TRANSMEM`	`124 149`	`26`	`Potential.`
`TRANSMEM`	`160 187`	`28`	`Potential.`
`TRANSMEM`	`192 220`	`29`	`Potential.`
`TRANSMEM`	`315 339`	`25`	`Potential.`
`REGION`	`340 449`	`110`	`Linker.`
`REGION`	`450 888`	`439`	`Catalytic.`
`ACT_SITE`	`559 559`		`Charge relay system.`
`ACT_SITE`	`691 691`		`Charge relay system.`
`ACT_SITE`	`767 767`		`Charge relay system.`
`ACT_SITE`	`866 866`		`Proton donor.`
`CARBOHYD`	`281 281`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`296 296`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`419 419`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`518 518`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`870 870`		`N-linked (GlcNAc...) (Potential).`
`VAR_SEQ`	`522 574`		`Missing (in isoform 2).`	`VSP_002207`
`VARIANT`	`638 638`	`1`	`I -> V (in dbSNP:rs5908 [NCBI]).`	`VAR_011954 [3D]`
`HELIX`	`445 448`	`4`
`HELIX`	`464 473`	`10`
`HELIX`	`478 480`	`3`
`HELIX`	`481 484`	`4`
`STRAND`	`485 487`	`3`
`HELIX`	`488 500`	`13`
`STRAND`	`503 505`	`3`
`HELIX`	`506 511`	`6`
`TURN`	`520 525`	`6`
`STRAND`	`528 546`	`19`
`STRAND`	`549 556`	`8`
`HELIX`	`562 574`	`13`
`TURN`	`575 577`	`3`
`STRAND`	`579 590`	`12`
`STRAND`	`593 595`	`3`
`HELIX`	`599 609`	`11`
`HELIX`	`612 623`	`12`
`STRAND`	`630 639`	`10`
`STRAND`	`642 650`	`9`
`HELIX`	`657 674`	`18`
`STRAND`	`679 683`	`5`
`HELIX`	`695 700`	`6`
`STRAND`	`703 712`	`10`
`HELIX`	`714 719`	`6`
`HELIX`	`725 736`	`12`
`HELIX`	`738 742`	`5`
`STRAND`	`746 752`	`7`
`HELIX`	`753 763`	`11`
`HELIX`	`768 770`	`3`
`HELIX`	`771 774`	`4`
`STRAND`	`777 788`	`12`
`STRAND`	`790 800`	`11`
`STRAND`	`804 806`	`3`
`HELIX`	`807 810`	`4`
`HELIX`	`812 820`	`9`
`HELIX`	`833 859`	`27`
`HELIX`	`866 869`	`4`

Sequence information

Length: 888 AA [This is the length of the unprocessed precursor]

Molecular weight: 97476 Da [This is the MW of the unprocessed precursor]

CRC64: 49B610DCCCFA26B6 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MLSRLFRMHG LFVASHPWEV IVGTVTLTIC MMSMNMFTGN NKICGWNYEC PKFEEDVLSS 

        70         80         90        100        110        120 
DIIILTITRC IAILYIYFQF QNLRQLGSKY ILGIAGLFTI FSSFVFSTVV IHFLDKELTG 

       130        140        150        160        170        180 
LNEALPFFLL LIDLSRASTL AKFALSSNSQ DEVRENIARG MAILGPTFTL DALVECLVIG 

       190        200        210        220        230        240 
VGTMSGVRQL EIMCCFGCMS VLANYFVFMT FFPACVSLVL ELSRESREGR PIWQLSHFAR 

       250        260        270        280        290        300 
VLEEEENKPN PVTQRVKMIM SLGLVLVHAH SRWIADPSPQ NSTADTSKVS LGLDENVSKR 

       310        320        330        340        350        360 
IEPSVSLWQF YLSKMISMDI EQVITLSLAL LLAVKYIFFE QTETESTLSL KNPITSPVVT 

       370        380        390        400        410        420 
QKKVPDNCCR REPMLVRNNQ KCDSVEEETG INRERKVEVI KPLVAETDTP NRATFVVGNS 

       430        440        450        460        470        480 
SLLDTSSVLV TQEPEIELPR EPRPNEECLQ ILGNAEKGAK FLSDAEIIQL VNAKHIPAYK 

       490        500        510        520        530        540 
LETLMETHER GVSIRRQLLS KKLSEPSSLQ YLPYRDYNYS LVMGACCENV IGYMPIPVGV 

       550        560        570        580        590        600 
AGPLCLDEKE FQVPMATTEG CLVASTNRGC RAIGLGGGAS SRVLADGMTR GPVVRLPRAC 

       610        620        630        640        650        660 
DSAEVKAWLE TSEGFAVIKE AFDSTSRFAR LQKLHTSIAG RNLYIRFQSR SGDAMGMNMI 

       670        680        690        700        710        720 
SKGTEKALSK LHEYFPEMQI LAVSGNYCTD KKPAAINWIE GRGKSVVCEA VIPAKVVREV 

       730        740        750        760        770        780 
LKTTTEAMIE VNINKNLVGS AMAGSIGGYN AHAANIVTAI YIACGQDAAQ NVGSSNCITL 

       790        800        810        820        830        840 
MEASGPTNED LYISCTMPSI EIGTVGGGTN LLPQQACLQM LGVQGACKDN PGENARQLAR 

       850        860        870        880 
IVCGTVMAGE LSLMAALAAG HLVKSHMIHN RSKINLQDLQ GACTKKTA

P04035 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools